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Abstract：
This study aims to assess the prognostic value of the C-C motif chemokine receptor (CCR) gene family in hepatocellular carcinoma (HCC) and its relationship with immune infiltration and molecular subtypes of HCC. The evaluation of the GSE14520 dataset and TCGA database confirmed the prognostic significance of CCR. Building upon the correlation between CCR1, CCR5, and CCR7 and favorable prognosis, we further validated the prognostic importance of CCR1, CCR5, and CCR7 in ICGC database and an independent cohort from Guangxi autonomous region. Then, we constructed a risk prognosis model. Additionally, we observed significant positive correlations between CCR1, CCR5, and CCR7 and the infiltration of B cells, T cells, and macrophages in HCC. Subsequently, we conducted CCK assays, Transwell assays, and colony formation assays to evaluate the molecular biological functions of CCR1, CCR5, and CCR7. These experiments further confirmed that upregulation of CCR1, CCR5, and CCR7 can individually inhibit the proliferation, migration, and stemness of HCC cells. By analyzing the relationship between expression levels and tumor mutation frequency, we discovered that patients with high CCR1 expression were more likely to be classified as non-proliferative HCC. Similar conclusions were observed for CCR5 and CCR7. The association of CCR1, CCR5, and CCR7 with the molecular subtypes of HCC suggests that they may serve as intermediary molecules linking immune status and molecular subtypes in HCC. In summary, CCR1, CCR5, and CCR7 have the potential to serve as prognostic biomarkers for HCC and regulate HCC progression by influencing immune cell infiltration.
摘要：
本研究旨在评估C-C基序趋化因子受体（CCR）基因家族在肝细胞癌（HCC）中的预后价值及其与HCC免疫浸润和分子亚型的关系。对GSE14520数据集和TCGA数据库的评估证实了CCR的预后意义。基于CCR1、CCR5和CCR7与良好预后的相关性，我们在ICGC数据库和来自广西自治区的独立队列中进一步验证了CCR1,CCR5和CCR7的预后重要性.然后，我们构建了风险预测模型。此外,CCR1、CCR5和CCR7与B细胞浸润呈显著正相关,T细胞,和巨噬细胞在HCC中。随后，我们进行了CCK检测,Transwell分析，和集落形成试验来评估CCR1、CCR5和CCR7的分子生物学功能。这些实验进一步证实，CCR1、CCR5和CCR7的上调可以单独抑制增殖，迁移,和肝癌细胞的干性。通过分析表达水平与肿瘤突变频率的关系,我们发现CCR1高表达的患者更有可能被归类为非增殖性HCC.对于CCR5和CCR7观察到类似的结论。CCR1，CCR5和CCR7与HCC分子亚型的关联表明，它们可能作为连接HCC免疫状态和分子亚型的中间分子。总之,CCR1，CCR5和CCR7有可能作为HCC的预后生物标志物，并通过影响免疫细胞浸润来调节HCC进展。
